The following cases and commentary, which address topics in endocrinology, are excerpted from ACP's Medical Knowledge Self- Assessment Program (MKSAP14).
Case 1: Hyperglycemia in a patient with bowel obstruction and sepsis
A 42-year-old man is evaluated in the emergency department for a two-day history of fever, confusion, and abdominal pain. His temperature is 38.4°C (101.1°F); cardiac examination is normal. Examination of the lungs reveals diffuse bilateral crackles. The abdomen is diffusely and markedly tender, with rebound and guarding. Leukocyte count is 18,400 cells/µL (18.4 ×109 cells/L) with 80% segmented neutrophils and 6% band forms. He has no history of diabetes, but his plasma glucose concentration in the emergency department is 205 mg/dL. Chest radiograph shows pulmonary edema.
The patient is hospitalized, imipenem/cilastatin is started, and a surgical consultation is made. The patient has a bowel obstruction and intra-abdominal source of severe sepsis, and after surgery he returns to the surgical intensive care unit.
Which of the following is the most appropriate management of the patient's hyperglycemia?
A. Treat if glucose level rises above 250 mg/dL
B. Subcutaneous regular insulin based on a sliding scale
C. Long-acting basal insulin
D. Intravenous insulin drip.
Case 2: Hyperglycemia after mitral valve replacement
A 57-year-old man develops fever two days after prosthetic mitral valve replacement. He remains intubated and requires pressors. Medications include epinephrine, dexamethasone, and famotidine. Other than a history of mitral valve stenosis, the patient had been previously healthy.
On examination, he has a rectal temperature of 38.5°C (101.3°F) and crackles in the left lung; leukocyte count is 12,600 cells/µL (12.6 × 109 cells/L) and plasma glucose level is 178 mg/dL (9.88 mmol/L); chest radiograph shows an infiltrate in the left lower lobe. Antibiotic therapy is started for suspected pneumonia.
Which of the following is the most appropriate management for this patient's hyperglycemia?
A. Intravenous insulin infusion
B. Regular insulin by sliding scale
C. Insulin glargine, 10 units in the evening
D. Glyburide, 5 mg/d
Case 3: Progressive obtundation
A 75-year-old woman is admitted to the medical intensive care unit with progressive obtundation. Physical examination reveals a nonarousable elderly women, with core temperature of 35°C (95°F), blood pressure of 104/84 mm Hg, and pulse rate of 48 beats/min. The patient weighs 82 kg (180 lb), and has a 4-cm transverse scar above the suprasternal notch, cold doughy skin, and delayed deep tendon reflex relaxation phase. The patient's medical records state that she is taking both digoxin and levothyroxine, but she has not been seen in more than a year. Serum sodium is 127 mEq/L (127 mmol/L); total cholesterol is 318 mg/dL (8.22 mmol/L). Digoxin is undetectable. Serum thyroid- stimulating hormone level is pending. Urinalysis shows too many leukocytes to count and gram-negative rods. Urine and blood cultures are pending.
Which of the following would be appropriate therapy at this time?
A. Levothyroxine, corticosteroids, empiric antibiotics
B. Levothyroxine alone
C. Levothyroxine and liothyronine
D. No therapy until TSH level is known
Case 4: Severe hypothyroidism
A 65-year-old man is hospitalized for treatment of severe hypothyroidism. He was doing well initially on thyroid hormone replacement therapy but experienced a syncopal episode when walking to the bathroom. The patient denies palpitations or chest pain.
On physical examination, the blood pressure is 80/60 mm Hg, and the pulse rate is 72 beats/min. He has jugular venous distension, diminished heart sounds, and a palpable liver edge below the right costal margin. Complete blood count and electrolytes are normal. Serum free T4 is 0.7 ng/dL (8.5 pmol/L) and serum TSH is 22 µU/mL (22 mU/L). Electrocardiography shows low voltage in all leads. Chest radiograph shows an enlarged cardiac silhouette.
Which of the following is the most likely cause of this patient's change in clinical status?
A. Adrenal insufficiency
E. Cardiac tamponade
Case 5: Hashimoto's thyroiditis
A 23-year-old woman is evaluated in the emergency department for nausea, anorexia, dizziness, and diffuse moderate abdominal discomfort. Three weeks ago, she had been evaluated for fatigue and cold intolerance and was noted to have a firm goiter, with the thyroid estimated to be twice the size expected in a woman of her build. Thyroid peroxidase antibodies were positive, and her serum thyroid-stimulating hormone (TSH) level was 20 µU/mL. Hashimoto's thyroiditis was diagnosed, and therapy with levothyroxine, 100 µg/d, was begun. In addition to her symptoms, she has had a 2-kg (4.5-lb) weight loss. In the emergency department, the blood pressure is 90/60 mm Hg; the pulse rate 100 beats/min, and she appears darkly pigmented. Laboratory results include serum sodium 132 mEq/L, potassium 5.0 mEq/L, TSH 6.0 µU/mL (6.0 mU/L), and thyroxine (T4) normal.
Which of the following would be the most appropriate next test in the evaluation of this patient?
A. Triiodothyronine (T3)
B. ACTH, cortisol followed by cosyntropin stimulation
C. Thyroid-stimulating immunoglobulins
D. 24-hour urine collection for free cortisol
Answers and commentary
Correct answer: D. Intravenous insulin drip.
Although the exact range/goal for the patient's target glucose level varies according to different guidelines, tight glucose control is now practiced widely in the intensive care unit. In 1,548 surgical ICU patients studied via a randomized, controlled trial, intensive insulin therapy with a goal of maintaining blood glucose levels between 80 mg/dL and 110 mg/dL resulted in a 34% reduction for in-hospital mortality (7.2% vs. 10.9%; P = 0.01). The patient should not be allowed to have hyperglycemia, which is believed to contribute to a host of physiologic derangements such as inflammation and coagulopathy that should be controlled in the septic patient. In fact, in the 2001 Van den Berghe study of patients in the surgical intensive care unit with and without sepsis, the greatest reductions in mortality occurred in those with sepsis and multiple organ dysfunction. In another study of a uniformly medical intensive care unit population, Van den Berghe and colleagues in 2006 found that intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical intensive care unit. In addition, other multicenter studies have been stopped early due to hypoglycemia and other adverse events occurring more commonly in the tight sugar group. The sepsis guidelines embraced a more modest goal of keeping critically ill patients' glucose levels below 150 mg/dL. Such levels are increasingly targeted now via insulin infusions and regular monitoring.
Subcutaneous regular insulin based on a sliding scale and long-acting basal insulin do not offer the best acute titration of glucose in ICU patients who may have volatile glucose levels. Both of these options should be reserved for the less acutely ill or more stable, non-ICU patient.
- Hyperglycemia should be treated in critically ill patients with aggressive insulin therapy to maintain tight glycemic control.
Correct answer: A. Intravenous insulin infusion.
Hyperglycemia after cardiac surgery and during critical illness is a strong predictor of adverse outcomes, including infectious complications and death. Randomized clinical trials have shown that aggressively treating hyperglycemia in this setting with intravenous insulin infusion reduces mortality. In a large, randomized, controlled study from a European surgical intensive care unit, normalizing blood glucose (80 to 110 mg/dL [4.44 to 6.11 mmol/L]) reduced intensive care unit mortality by 42%, mainly in patients who were in intensive care for more than five days and patients who developed infection. Aggressive control of hyperglycemia is now recommended by several professional organizations, with most recommending a blood glucose target of 110 mg/dL (6.11 mmol/L) or less.
Regular insulin by intermittent sliding scale will not allow for sufficient glycemic control in the intensive care unit setting and has been associated with more hyperglycemic and hypoglycemic events in hospitalized patients. Insulin glargine also can only be adjusted once every 24 hours and will similarly not allow for sufficient glycemic control. Oral agents, such as glyburide, are inappropriate in this setting.
- Hyperglycemia after cardiac surgery and during critical illness is a strong predictor of adverse outcomes, including infectious complications and death.
- Intravenous insulin infusion in hyperglycemic patients in the intensive care unit improves outcomes.
Correct answer: A. Levothyroxine, corticosteroids, empiric antibiotics.
This patient has myxedema coma. The diagnosis is made clinically and there are many clues in this case history including numerous physical examination findings of hypothyroidism, a thyroidectomy scar, and evidence of noncompliance with medication (hence her undetectable digoxin levels). Since infection is a common precipitant of myxedema coma, pan-culture and empiric antibiotic therapy with broad-spectrum antibiotics are generally recommended. Corticosteroids are given prophylactically in case of concurrent adrenal insufficiency, which might otherwise become manifest as replacement thyroid hormone therapy is begun.
- Infection is a common precipitant of myxedema coma, and pan-culture and empiric antibiotic therapy with broadspectrum antibiotics are recommended for all affected patients.
Correct answer: E. Cardiac tamponade.
This patient has developed cardiac tamponade due to a large pericardial effusion. Pericardial effusion is a known consequence of moderate to severe hypothyroidism and is suggested in this case by the patient's diminished heart sounds, low voltage on electrocardiography, and an enlarged cardiac silhouette on chest radiograph. Acute adrenal insufficiency may develop in patients begun on levothyroxine therapy in the setting of unrecognized chronic adrenal insufficiency, but other than hypotension, the clinical clues do not support this diagnosis. Although this patient is at risk for developing ischemia as the thyroid hormone levels are increased, nothing in the scenario points to this diagnosis either. The “hypothyroid heart” refers to decreased contractility and pulse rate—both contributing to a decreased cardiac output at a time when peripheral vascular resistance is increased. The patient is at risk for cardiomyopathy and congestive heart failure through these mechanisms, but nothing in the scenario suggests this etiology for his decline in cardiac function.
- Pericardial effusion is a consequence of moderate to severe hypothyroidism and is indicated by diminished heart sounds, low voltage on electrocardiography, and an enlarged cardiac silhouette.
- The “hypothyroid heart” refers to decreased contractility and pulse rate—both contributing to a decreased cardiac output at a time when peripheral vascular resistance is increased.
Correct answer: B. ACTH, cortisol followed by cosyntropin stimulation.
The patient has hypothyroidism due to autoimmune destruction of the thyroid, a form of chronic lymphocytic thyroiditis. She is treated appropriately with levothyroxine, and her TSH begins to return to normal concentrations, signifying replenishment of thyroxine deficiency.
Unfortunately, the patient has an additional unsuspected autoimmune process: destruction of the adrenal cortex. When autoimmune processes result in concomitant thyroid and adrenal failure, the clinical complex is referred to as Schmidt's syndrome. Adrenal failure is often unrecognized initially, since low thyroxine concentration results in depressed metabolic clearance of diminished cortisol levels. As thyroxine deficiency is corrected, metabolic rate increases, cortisol is cleared and the damaged zona fasciculata is unable to compensate with cortisol production. The patient subsequently develops clinical adrenal insufficiency and requires glucocorticoid supplementation. Antibodies to the 21-hydroxylase enzyme (CYP21) are frequently present in patients with autoimmune adrenal insufficiency.
Primary adrenal insufficiency results in loss of all three layers of the adrenal cortex, causing insufficient aldosterone, cortisol, and androgen secretion. The patient experiences a decrease in cardiac output, increased secretion and renal response to arginine vasopressin, and diminished renal clearance of potassium. Free water retention results in hyponatremia. The patient is hyperkalemic, hypotensive, and mildly hypoglycemic.
Diagnosis is made with a cosyntropin stimulation test, and hydrocortisone, 20 mg in the morning and 5 to 10 mg in the evening, is required after therapy for acute adrenal insufficiency is administered.
Thyroid-stimulating immunoglobulins are associated with autonomous thyroid function (Graves' disease). Triiodothyronine concentrations would be expected to be low or normal, but this offers little discriminatory information.
- In patients with concomitant autoimmune adrenal and thyroid failure (Schmidt's syndrome), adrenal failure is often unrecognized initially; as thyroxine deficiency is corrected, the patient develops clinical adrenal insufficiency, requiring glucocorticoid supplementation.